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1.
Life Sci ; 330: 121991, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37524161

RESUMO

Dysfunction of mesangial cells plays a significant role in the glomerular lesions and is implicated in the pathophysiology of diabetic nephropathy (DN). Macrophages infiltration is the main pathological feature of DN, which can ultimately lead to renal inflammation. Recent studies suggest that the crosstalk between kidney resident cells and inflammatory cells influences the development of DN, and that controlling this crosstalk may help treat DN. Here, we found that DN mice appeared renal pathological damage, including dilation of mesangial matrix and significant infiltration of macrophages, accompanied by increased inflammatory response, NLRP3 inflammasome activation and autophagy deficiency. Additionally, mesangial cells internalized exosomes from high glucose (HG) treated macrophage, resulting the activation of inflammatory cytokines and NLRP3 inflammasome and deficiency of autophagy in vitro and in vivo. Moreover, C57BL/6 mice injected HG-stimulated macrophages-derived exosomes exhibited renal dysfunction and mesangial matrix expansion. Taken together, the present study demonstrated that mesangial cells responded to HG treated macrophage-derived exosomes by promoting the activation of NLRP3 inflammasome and autophagy deficiency, thereby participating in the development of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Exossomos , Camundongos , Animais , Inflamassomos , Nefropatias Diabéticas/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Células Mesangiais , Exossomos/patologia , Camundongos Endogâmicos C57BL , Autofagia , Macrófagos/patologia
2.
Phytomedicine ; 107: 154477, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36215790

RESUMO

BACKGROUND: Danshen injection (DSI) is an agent extracted from the Salvia miltiorrhiza Bunge, a natural drug commonly used to alleviate kidney diseases. However, the material basis and therapeutic effects of DSI on nephrotic syndrome (NS) remain unclear. PURPOSE: To investigate the material basis of DSI and the therapeutic effects and underlying mechanisms of NS. METHODS: NS models were established using adriamycin-induced BALB/c mice and lipopolysaccharide-induced mouse podocytes (MPC-5). Following DSI and prednisone administration, kidney coefficients, 24 h urine protein, blood urea nitrogen, and serum creatinine levels were tested. Histomorphology was observed by periodic acid-Schiff staining and hematoxylin and eosin staining of the kidney sections. The glomerular basement membrane and autophagosomes of the kidneys were observed using transmission electron microscopy. Nephrin and desmin levels in the glomeruli were tested using immunohistochemistry. The viability of MPC-5 cells was tested using cell counting kit-8 after chloroquine and rapamycin administration in combination with DSI. The in vivo and in vitro protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, phosphorylated AKT (Ser473), mammalian target of rapamycin (mTOR), microtubule-associated protein light chain 3 (LC3), beclin1, cleaved caspase-3, and caspase-3 were detected using western blotting. RESULTS: Our results showed that DSI contained nine main components: caffeic acid, danshensu, lithospermic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D, and 3, 4-Dihydroxybenzaldehyde. In in vivo studies, the NS mice showed renal function and pathological impairment. Podocytes were damaged, with decreased levels of autophagy and apoptosis, accompanied by inhibition of the PI3K/AKT/mTOR signaling. DSI administration resulted in improved renal function and pathology in NS mice, with the activation of autophagy and PI3K/AKT/mTOR signaling in the kidneys. Additionally, podocytes were less damaged and intracellular autophagosomes were markedly increased. In vitro studies have shown that DSI activated MPC-5 autophagy and reduced apoptosis via the PI3K/AKT/mTOR pathway. CONCLUSION: Collectively, this study demonstrated that DSI activated podocyte autophagy and reduced apoptosis via the PI3K/AKT/mTOR signaling, ultimately attenuating NS. Our study clarified the main components of DSI and elucidated its therapeutic effects and potential mechanisms for NS, providing new targets and agents for the clinical treatment of NS.


Assuntos
Síndrome Nefrótica , Podócitos , Salvia miltiorrhiza , Animais , Autofagia , Proteína Beclina-1/metabolismo , Caspase 3/metabolismo , Cloroquina/farmacologia , Creatinina , Desmina/metabolismo , Desmina/farmacologia , Doxorrubicina/farmacologia , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Lipopolissacarídeos/farmacologia , Mamíferos/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/metabolismo , Ácido Periódico/metabolismo , Ácido Periódico/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Podócitos/metabolismo , Prednisona/metabolismo , Prednisona/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo
3.
BMC Nephrol ; 23(1): 303, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064366

RESUMO

BACKGROUND: Increasing evidence suggests that immune cell infiltration contributes to the pathogenesis and progression of diabetic nephropathy (DN). We aim to unveil the immune infiltration pattern in the glomerulus of DN and provide potential targets for immunotherapy. METHODS: Infiltrating percentage of 22 types of immune cell in the glomerulus tissues were estimated by the CIBERSORT algorithm based on three transcriptome datasets mined from the GEO database. Differentially expressed genes (DEGs) were identified by the "limma" package. Then immune-related DEGs were identified by intersecting DEGs with immune-related genes (downloaded from Immport database). The protein-protein interactions of Immune-related DEGs were explored using the STRING database and visualized by Cytoscape. The enrichment analyses for KEGG pathways and GO terms were carried out by the gene set enrichment analysis (GSEA) method. RESULTS: 11 types of immune cell were revealed to be significantly altered in the glomerulus tissues of DN (Up: B cells memory, T cells gamma delta, NK cells activated, Macrophages.M1, Macrophages M2, Dendritic cells resting, Mast cells resting; Down: B cells naive, NK cells resting, Mast cells activated, Neutrophils). Several pathways related to immune, autophagy and metabolic process were significantly activated. Moreover, 6 hub genes with a medium to strong correlation with renal function (eGFR) were identified (SERPINA3, LTF, C3, PTGDS, EGF and ALB). CONCLUSION: In the glomerulus of DN, the immune infiltration pattern changed significantly. A complicated and tightly regulated network of immune cells exists in the pathological of DN. The hub genes identified here will facilitate the development of immunotherapy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Biologia Computacional/métodos , Nefropatias Diabéticas/patologia , Perfilação da Expressão Gênica/métodos , Humanos , Glomérulos Renais/patologia , Transcriptoma
4.
Bioengineered ; 13(5): 13956-13969, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35723058

RESUMO

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 ß, IL-2, IL-6, TNF-α and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.


Assuntos
Glomerulonefrite Membranosa , MicroRNAs , Animais , Antagomirs , Autofagia , Benzofuranos , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/genética , Inflamação , Rim/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
5.
J Ovarian Res ; 13(1): 78, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32682445

RESUMO

OBJECTIVES: We sought to determine the impact of pretreatment plasma platelet levels, dimerized plasmin fragment (D-dimer) and fibrinogen in recurrent epithelial ovarian cancer (EOC) and the impact of platelet levels on SKOV3 cell lines growth and responsiveness to chemotherapy. METHODS: Under approval of ethical committee, we identified 104 women with recurrent EOC who underwent treatment between January 2010 and February 2015. Reviewing clinical, laboratory, and pathologic records from this retrospective cohort, we analyzed the correlation between pretreatment plasma D-dimer, fibrinogen, platelet levels and clinicopathological parameters, progression free survival (PFS) and overall survival (OS). Inco-culture experiments human ovarian cancer SKOV3 cell lines were used to test the effect of platelet levels on tumor growth and responsiveness to docetaxel. RESULTS: Of the 104 recurrent EOC, thrombocytosis at diagnosis and the decrease of platelet count by less than 25% after primary therapy were associated with worse median progression free survival (P = 0.003;P = 0.021) and median overall survival (P = 0.009;P = 0.009). Mean platelet levels declined at the end of primary therapy(P < 0.001) and rose at recurrence(P = 0.007). In multivariate analysis, elevated platelet levels at primary therapy and the decrease of platelet count less than 25% after primary therapy were unfavorable prognostic factor for PFS(P = 0.022; P = 0.015) and OS(P = 0.013;P = 0.007) in recurrent EOC, but elevated plasma D-dimer and fibrinogen were not. In SKOV-3 ovarian cancer cell lines, suitable concentration platelet co-culture protected against apoptosis (P < 0.05). CONCLUSIONS: Platelet count during treatment could be used as a biomarker used for monitoring the disease recurrence and predicting treatment response. And platelet with suitable concentration co-culture protected against apoptosis in SKOV3 cell line, which may explain clinical observations.


Assuntos
Biomarcadores Tumorais/metabolismo , Plaquetas/patologia , Carcinoma Epitelial do Ovário/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Ovário/patologia , Contagem de Plaquetas/métodos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
6.
J Ovarian Res ; 13(1): 46, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334618

RESUMO

OBJECTIVES: For patients presenting with adnexal mass, it is important to correctly distinguish whether the mass is benign or malignant for the purpose of precise and timely referral and implication of correct line of management. The objective of this study was to evaluate the performance of Risk of malignancy Indexes (RMI) 1-4, Human Epididymis Protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA) in differentiating the adnexal mass into benign and malignant. METHODS: A retrospective study using 155 patients diagnosed with adnexal mass between January 2014 to December 2014 in The First Affiliated Hospital of Zhengzhou University was conducted. The patient records were assessed for age, menopausal status, serum CA125 and HE4 levels, ultrasound characteristics of the pelvic mass and the final pathological diagnosis of the mass. RMI1, RMI2, RMI3, RMI4, ROMA were calculated for each patient and the sensitivity, specificity and the Receiver Operating Characteristics (ROC) curves were determined for each test to evaluate their performance. RESULTS: Among 155 patients with adnexal masses meeting inclusion criteria, 120 (77.4%) were benign, 8 (5.2%) borderline and 27 (17.4%) were malignant. RMI2 and RMI4 had the highest sensitivity (66.7%) while HE4 had the highest specificity (96.9%).Although ROMA had the highest area under the curve (AUC) of 0.886 it was not found to be statistically superior to the other tests. For epithelial ovarian cancers, ROMA (80%), HE4 (96.9%) and RMI 4 (0.868) had the highest sensitivity, specificity and AUC respectively however, the AUC characteristics were not statistically significant between any groups. Compared to the postmenopausal group (sensitivity 72.2-77.8%) all the tests showed lower sensitivity (42.9%) for the premenopausal group of patients. CONCLUSIONS: RMI 1-4, ROMA and HE4 were all found to be useful for differentiating benign/borderline adnexal masses from malignant ones for deciding optimal therapy, however no test was found to be significantly better than the other. None were able to differentiate between benign and borderline tumors. All of the tests demonstrated increased sensitivity when borderline tumors were considered low-risk, and when only epithelial ovarian cancers were considered.


Assuntos
Doenças dos Anexos/patologia , Algoritmos , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Neoplasias/patologia , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Doenças dos Anexos/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/sangue , Fatores de Risco , Triagem , Adulto Jovem
7.
Molecules ; 24(5)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845646

RESUMO

Microencapsulated phase change materials (MicroPCMs)-incorporated in epoxy composites have drawn increasing interest due to their promising application potential in the fields of thermal energy storage and temperature regulation. However, the study on the effect of MicroPCMs on their microstructure, thermal and viscoelastic properties is quite limited. Herein, a new type of smart epoxy composite incorporated with polyurea (PU)-shelled MicroPCMs was fabricated via solution casting method. Field emission-scanning electron microscope (FE-SEM) images revealed that the MicroPCMs were uniformly distributed in the epoxy matrix. The thermal stabilities, conductivities, phase change properties, and dynamic mechanical behaviors of the composite were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), thermal constant analyzer and infrared thermography. The results suggested that the heat storage ability of the composites was improved by increasing the MicroPCMs content. The thermal stability of MicroPCMs was found to be enhanced after incorporation into the matrix, and the MicroPCMs-incorporated epoxy composites showed a good thermal cycling reliability. Moreover, the incorporation of MicroPCMs reduced the composites' storage modulus but increased the glass transition temperature (Tg) as a result of their restriction to the chain motion of epoxy resin. Besides, a less marked heating effect for the composite was explored through infrared thermography analysis, demonstrating the good prospect for temperature regulation application.


Assuntos
Cápsulas/síntese química , Resinas Epóxi/química , Transição de Fase , Alcanos/química , Emulsões/química , Temperatura Alta , Cinética , Teste de Materiais/métodos , Fenômenos Mecânicos , Tamanho da Partícula , Reprodutibilidade dos Testes , Propriedades de Superfície , Temperatura , Termodinâmica
8.
J Fluoresc ; 26(1): 43-51, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26531213

RESUMO

(E)-N-((8-Hydroxy-1,2,3,5,6,7-hexahydropyrido-[3,2,1-ij]-quinolin-9-yl)methylene)-4-tert-butyl -benzhydrazide has been developed as a single, dual-functional chemosensor. The chemosensor showed a good selectivity and sensitivity toward to Al(3+) and Cu(2+) at a low detection limit, respectively. Theoretical calculations have also been carried out to understand the configuration of the complexes.


Assuntos
Alumínio/análise , Cobre/análise , Corantes Fluorescentes/química , Piridinas/química , Quinolinas/química , Água/química , Estrutura Molecular , Piridinas/síntese química , Quinolinas/síntese química , Espectrofotometria
9.
Org Biomol Chem ; 12(38): 7494-7, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25162723

RESUMO

A new and mild method for the efficient synthesis of 3,3-dichloro-2-sulfonyliminoindolines via AcOH-mediated dichloroimination of indoles using chloramine-B is presented. Application of this method to the efficient construction of pyrrolidinoindoles and N-C3 linked pyrrolidinoindolines is demonstrated.


Assuntos
Ácido Acético/química , Cloraminas/química , Cloro/química , Iminas/química , Indóis/química , Catálise
10.
J Dent ; 42 Suppl 1: S30-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24993853

RESUMO

OBJECTIVES: To investigate in vitro and in situ the deposition and formation of hydroxyapatite (HAP) on enamel surfaces following brushing with a novel toothpaste containing calcium silicate (CaSi), sodium phosphate salts and fluoride. METHODS: Polished enamel blocks were brushed in vitro with a slurry of the CaSi toothpaste. After one brush and four weeks simulated brushing the enamel surfaces were analysed. In an in situ protocol, enamel blocks were attached to first or second molar teeth of healthy subjects, exposed to 4 weeks twice per day brushing with the CaSi toothpaste and then analysed. The surface deposits were analysed using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM) and selected area electron diffraction (SAED). In addition, the CaSi toothpaste was slurried in simulated oral fluid (SOF) over a 3 hour period and the solids were isolated and analysed by Fourier transform infrared spectroscopy (FTIR). RESULTS: The FTIR study demonstrated that calcium phosphate phases had formed and these became increasingly crystalline over 3 hours. CaSi was deposited onto enamel surfaces following one brushing with the toothpaste in vitro.The deposited particles showed evidence of HAP crystalline phases associated with the CaSi. Following 4 weeks brushing in vitro, the deposition increased and analyses showed that the deposited material was HAP. These results were confirmed by the in situ study. CONCLUSIONS: Calcium silicate can be deposited onto enamel surfaces from a novel toothpaste formulation where it can form the enamel mineral HAP. CLINICAL SIGNIFICANCE: A novel toothpaste formulation containing CaSi can form HAP on enamel surfaces. The potential of this technology is for a novel approach to the repair of demineralised enamel and the protection of enamel during acid exposure.


Assuntos
Compostos de Cálcio/farmacologia , Esmalte Dentário/efeitos dos fármacos , Durapatita/química , Fluoretos/farmacologia , Fosfatos/farmacologia , Silicatos/farmacologia , Cremes Dentais/farmacologia , Animais , Cálcio/química , Fosfatos de Cálcio/química , Bovinos , Cristalografia , Esmalte Dentário/química , Película Dentária/química , Seguimentos , Humanos , Técnicas In Vitro , Teste de Materiais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Distribuição Aleatória , Saliva Artificial/química , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de Tempo , Escovação Dentária/instrumentação , Escovação Dentária/métodos
11.
J Biomed Nanotechnol ; 10(6): 1091-104, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24749403

RESUMO

Copolymer composite scaffolds and bioceramic/polymer composite scaffolds are two representative forms of composite scaffolds used for bone tissue engineering. Studies to compare biocompatibility and bone-repairing effects between these two scaffolds are significant for selecting or improving the scaffold for clinical application. We prepared two porous scaffolds comprising poly-lactic-acid/poly-glycolic-acid (PLGA) and poly-lactic-acid/nano-hydroxyapatite (nHAP/PLA) respectively, and examined their biocompatibility with human bone marrow-derived mesenchymal stem cells (hMSCs) through evaluating adhesion, proliferation and osteogenic differentiation potentials of hMSCs in the scaffold. Then, the PLGA scaffold with hMSCs (PM construct) and the nHAP/PLA scaffold with hMSCs (HPM construct) were transplanted into the rat calvarial defect areas to compare their effects on the bone reconstruction. The results showed that the nHAP/PLA scaffold was in favor of adhesion, matrix deposition and osteogenic differentiation of hMSCs. For in vivo transplantation, both HPM and PM constructs led to mineralization and osteogenesis in the defect area of rat. However, the area grafted with PM construct showed a better formation of mature bone than that with HPM construct. In addition, the evaluation of in vitro and in vivo degradation indicated that the degradation rate of nHAP/PLA scaffold was much lower than that of PLGA scaffold. It is inferred that the lower degradation of nHAP/PLA scaffold should result in its inferior bone reconstruction in rat calvaria. Therefore, the preparation of an ideal composite scaffold for bone tissue engineering should be taken into account of the balance between its biocompatibility, degradation rate, osteoconductivity and mechanical property.


Assuntos
Regeneração Óssea/fisiologia , Substitutos Ósseos/administração & dosagem , Durapatita/administração & dosagem , Ácido Láctico/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Polímeros/administração & dosagem , Fraturas Cranianas/terapia , Alicerces Teciduais , Animais , Substitutos Ósseos/efeitos adversos , Substitutos Ósseos/química , Durapatita/efeitos adversos , Durapatita/química , Ácido Láctico/efeitos adversos , Ácido Láctico/química , Masculino , Poliésteres , Ácido Poliglicólico/efeitos adversos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/efeitos adversos , Polímeros/química , Porosidade , Ratos , Fraturas Cranianas/patologia , Resultado do Tratamento
12.
Se Pu ; 31(7): 714-7, 2013 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-24164044

RESUMO

A novel poly( 4-vinylphenylboronic acid (VPBA) -co-pentaerythritol triacrylate (PETA)) monolithic column was prepared by thermal-initiated copolymerization of VPBA and PETA in a binary porogen system comprising diethylene glycol and ethylene glycol. The fabricated monolithic column demonstrated good boronate affinity property, which can specifically capture cis-diols containing compounds. We developed such a monolithic column and applied it to enrich active components in Herba Taraxaci and Euonymus acanthocarpus. The extracts of the two traditional Chinese medicines were separated and enriched on microHPLC by the prepared monolith, and the fractions were collected and examined by HPLC. The results showed that the responses of the corresponding peaks were greatly improved, indicating that the poly( VPBA-co-PETA) monolithic column can be efficiently used to enrich active components in traditional Chinese medicines containing cis-diols group.


Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Acrilatos , Ácidos Borônicos , Medicina Tradicional Chinesa , Propilenoglicóis , Compostos de Vinila
13.
Acta Biomater ; 7(8): 3042-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21569871

RESUMO

Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including ß-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 µm, and the biomimetic HAP Ostim35®). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P=0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.


Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Fosfatos de Cálcio/química , Coristoma/patologia , Portadores de Fármacos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Osteogênese/efeitos dos fármacos , Animais , Coristoma/diagnóstico por imagem , Durapatita/química , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/patologia , Humanos , Masculino , Minerais/metabolismo , Músculos/diagnóstico por imagem , Músculos/efeitos dos fármacos , Nanoestruturas/ultraestrutura , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada por Raios X
14.
Biomed Mater ; 5(4): 041001, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20603529

RESUMO

It is widely agreed that nano-calcium phosphates (CaP) play an important role in tissue engineering and medical application due to their unique biological characteristics. However, the properties of nano-CaP, including bioactivity, biocompatibility and mechanical properties, are tailored over wide ranges by controlling the size and morphology of particles. Therefore, it is important to develop synthesis methods which can control the particle size distribution and shape uniformly. In this study, we report that polyacrylic acid (PAA) can act as an efficient agent to modulate nano-CaP formation. The dimension of the resultant sphere-like nanoparticles (5-60 nm) can readily be regulated by changing PAA concentrations (75-200 microg ml(-1)). In contrast to other additives, PAA is a water-soluble polymer that has already been used as an excellent biocompatible implant material in vivo. Our in vitro proliferation experiments of bone marrow mesenchymal stem cells (BMSCs) demonstrate that the involvement of PAA does not change the bioactivity of the resultant nano-CaP. In contrast, the nano-CaP fabricated by using another typical control agent, hexadecyl (cetyl) trimethyl ammonium bromide, suppressed the cell proliferation of BMSCs. Thus, we suggest that the biopolymer, PAA, can provide a more biologically friendly pathway to prepare biological nano-CaP for biomedical application.


Assuntos
Fosfatos de Cálcio/química , Cristalização/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Nanotecnologia/métodos , Tamanho da Partícula , Coelhos , Transdução de Sinais/fisiologia , Propriedades de Superfície
15.
Zhonghua Nei Ke Za Zhi ; 48(1): 10-2, 2009 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19484969

RESUMO

OBJECTIVE: To investigate insulin resistance in type 1 diabetes (T1DM) with euglycemic-hyperinsulinemic clamp. METHODS: Eight cases of newly diagnosed T1DM and 8 cases of newly diagnosed type 2 diabetes (T2DM) were selected. Their insulin sensitivity index (ISI) was evaluated with euglycemic-hyperinsulinemic clamp after 2 week insulin intensive treatment and compared with that of 10 healthy volunteers (normal control group, NC group). RESULTS: Age, BMI, fasting insulin (FIns), fasting C-peptide in the T1DM group were significantly lower than those in the NC group, while waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, HDL-C were not significantly different between the T1DM and NC groups. Age, BMI, WHR, FIns, fasting C-peptide, SBP, TC, TG in the T1DM group were significantly lower than those in the T2DM group. The ISI of the NC, T1DM and T2DM groups were 12. 83 +/- 1.09, 9.95 +/-0.50, 3.80 +/- 0.20, respectively. There was significant difference among the three groups (P < 0.05). CONCLUSION: The ISI in T1DM was significantly lower than that in NC group, but higher than that in T2DM.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Técnica Clamp de Glucose , Resistência à Insulina , Adolescente , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Relação Cintura-Quadril , Adulto Jovem
16.
Zhonghua Nei Ke Za Zhi ; 46(7): 559-61, 2007 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-17959079

RESUMO

OBJECTIVE: To investigate the state of insulin secretion and insulin resistance in patients of Graves disease (GD) with impaired glucose tolerance (IGT) by hyperglycemic clamp. METHODS: Six cases of Graves disease with IGT were selected as GD + IGT group and ten healthy volunteers as normal control group (NC group). All the subjects were required to fast for 12 hours and then underwent hyperglycemic clamp to assay insulin secretion and insulin sensitivity. Glutamic acid decarboxylase antibody (GAD-A) was tested in all the subjects. RESULTS: Insulin secretion in GD + IGT group was significantly higher than that in NC group. The 1st phase insulin secretion (1PH) was (636.31 +/- 105.54) mIU/L vs (233.56 +/- 21.33) mIU/L, P = 0.001. The 2nd phase insulin secretion (2PH) was (146.68 +/- 25.00) mIU/L vs (67.06 +/- 6.23) mIU/L, P = 0.03. The maximal insulin secretion during 120 - 150 minutes (Ins(120 - 150)) was (195.05 +/- 32.94) mIU/L vs (87.64 +/- 9.78) mIU/L, P = 0.04. The hyperglycemic clamp insulin sensitivity index (average glucose metabolic rate during 120 - 150 minutes/Ins(120 - 150)) was significantly lower in GD + IGT group than that in NC group (11.52 +/- 1.90 vs 21.72 +/- 3.25, P = 0.04). GAD-A was negative in all subjects. CONCLUSION: Cases of GD with IGT show significant insulin resistance with compensated elevated insulin secretion.


Assuntos
Intolerância à Glucose/sangue , Doença de Graves/fisiopatologia , Resistência à Insulina , Insulina/sangue , Adulto , Glicemia/metabolismo , Feminino , Técnica Clamp de Glucose , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Doença de Graves/sangue , Doença de Graves/metabolismo , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Pessoa de Meia-Idade
17.
Zhonghua Nei Ke Za Zhi ; 45(8): 646-9, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17074149

RESUMO

OBJECTIVE: To evaluate the function of the first phase of insulin secretion of pancreatic B cells in newly diagnosed type 2 diabetics using nateglinide-intravenous glucose insulin release test (NG-IVGIRT). METHODS: NG-IVGIRT and intravenous glucose insulin release test (IVGIRT) were done in 8 patients with newly diagnosed type 2 diabetes mellitus and NG-IVGIRT was done in 8 normal people. Insulin and glucose of blood were determined at - 15, 0, 2, 4, 6, 8 and 10 min in NG-IVGIRT or IVGIRT. RESULTS: The response of 0 - 10 min insulin to NG-IVGIRT was significantly higher than that to IVGIRT in the diabetics. The response of insulin to NG-IVGIRT in the normal controls was much higher than that in the diabetics. The area under curve (AUC) of insulin to NG-IVGIRT was apparently elevated and the AUC of glucose to NG-IVGIRT reduced in the normal controls as compared with those in the diabetics. CONCLUSION: The results indicated that the reserve of first phase insulin secretion in newly diagnosed type 2 diabetics could be provoked in some degree by NG-IVGIRT and there was a big difference in the reserve of the first phase of insulin secretion provoked by NG-IVGIRT between newly diagnosed type 2 diabetics and normal people.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Tolerância a Glucose , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adulto , Estudos de Casos e Controles , Cicloexanos/farmacologia , Estudos de Avaliação como Assunto , Feminino , Glucose/farmacologia , Teste de Tolerância a Glucose/normas , Humanos , Hipoglicemiantes/farmacologia , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia
18.
Zhonghua Shao Shang Za Zhi ; 18(3): 142-4, 2002 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12460507

RESUMO

OBJECTIVE: To explore the therapeutic effects of partial liquid ventilation on canine inhalation injury. METHODS: Mongrel dogs were inflicted with steam inhalation injury and were employed as the model. Partial liquid ventilation was accomplished by slow instillation of into the lungs. The changes in blood superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and arterial oxygen pressure (PaO(2)) were determined. RESULTS: The blood levels of MDA and NO at 2 postburn hours (PBHs) increased obviously but those of SOD and PaO(2) decreased significantly when compared with those before injury (P < 0.05). The blood levels of SOD, MDA, NO and PaO(2) recovered to near preinjury levels after partial liquid ventilation. CONCLUSION: Partial liquid ventilation might be helpful in the management of inhalation injury by raising blood oxygen pressure, antagonizing lipid peroxidation and reducing the in vivo NO production.


Assuntos
Queimaduras por Inalação/terapia , Óxido Nítrico/sangue , Espécies Reativas de Oxigênio/sangue , Animais , Monitorização Transcutânea dos Gases Sanguíneos , Pressão Sanguínea , Queimaduras por Inalação/sangue , Queimaduras por Inalação/fisiopatologia , Modelos Animais de Doenças , Cães , Feminino , Masculino , Malondialdeído/sangue , Oxigênio/metabolismo
19.
Zhonghua Shao Shang Za Zhi ; 18(2): 81-3, 2002 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12515651

RESUMO

OBJECTIVE: To explore the preventive effect of lanthanum chloride on enteral bacterial translocation in scalded rats. METHODS: Ninety Sprague-Dawley (SD) rats were employed in the study and randomly divided into three groups, i.e. normal control (A), burn control (B) and treatment (C) groups. Plasmid PUC19 labelled by JM109 was transfected to Escherichia coli (E. coli), so that restriction endonuclease finger - print image spectrum analysis could be applied to the tracing and quantification of the translocation of E. coli from intestine to mesenteric lymph nodes (MLNs) and blood. The intestinal tissue contents of endotoxin (ET), nitric oxide (NO), nitric oxide synthase (NOS), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. RESULTS: It was identified that the bacteria in MLNs and blood exhibited the same gene map with those from gastric gavage in B and C groups. But the bacterial quantity in MLNs in C group on 3 postburn day (PBD) was much lower than that in B group (P < 0.05). The intestinal MDA content in C group on 1 and 3 PBDs was obviously higher than that in B group (P < 0.05). CONCLUSION: Bacteria (E. coli) could be translocated from gut to MLNs and blood, which could be evidently alleviated by lanthanum chloride by means of its bactericidal property, inhibition of NOS activity, so that NO production decreased, and its ability to increase SOD activity leading to less production of MDA.


Assuntos
Queimaduras/tratamento farmacológico , Infecções por Escherichia coli/prevenção & controle , Escherichia coli/efeitos dos fármacos , Lantânio/farmacologia , Animais , Queimaduras/microbiologia , Endotoxinas/sangue , Endotoxinas/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/microbiologia , Feminino , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Linfonodos/efeitos dos fármacos , Linfonodos/microbiologia , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Mesentério/efeitos dos fármacos , Mesentério/microbiologia , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/sangue , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
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